{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:06Z","timestamp":1760060646879,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:00:00Z","timestamp":1757203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Landes-Offensive zur Entwicklung Wissenschaftlich-\u00f6konomischer Exzellenz (LOEWE) of the State of Hessen","award":["TP 7"],"award-info":[{"award-number":["TP 7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The hepatitis D virus (HDV) is a small, defective RNA virus that induces the most severe form of viral hepatitis. Despite its severity, HDV infections are under-diagnosed due to non-standardized and costly diagnostic screening methods. However, limited research has been conducted on characterizing HDV-specific antibodies as alternative tools for diagnosis. Thus, we generated HDV-specific, polyclonal antibodies by immunizing rabbits with the HDV protein, small hepatitis delta antigen (SHDAg), in its oligomeric or denatured form. We identified SHDAg-specific linear epitopes by peptide array analysis and compared them to epitopes identified in HDV-infected patients. Using in silico structural analysis, we show that certain highly immunogenic domains in SHDAg, such as the coiled-coil domain, are masked in the oligomeric conformation of the protein; others, such as the second arginine-rich motif, are exposed. The nuclear localization signal is presumably exposed only by specific interaction of oligomeric HDAg with the HDV-RNA genome. Through surface plasmon resonance analysis, we identified two polyclonal antibodies derived from rabbit antisera with affinities in the lower nanomolar range. These antibodies were used to establish an ELISA that can quantitatively detect HDV virions in vitro and upon further optimization could be used as a promising alternative diagnostic screening method.<\/jats:p>","DOI":"10.3390\/v17091220","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T08:06:32Z","timestamp":1757318792000},"page":"1220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation and Characterization of HDV-Specific Antisera with Respect to Their Application as Specific and Sensitive Research and Diagnostic Tools"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1381-8093","authenticated-orcid":false,"given":"Keerthihan","family":"Thiyagarajah","sequence":"first","affiliation":[{"name":"Research Group, Paul-Ehrlich-Institute, 63225 Langen, Germany"},{"name":"Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60329 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-4538","authenticated-orcid":false,"given":"Sascha","family":"Hein","sequence":"additional","affiliation":[{"name":"Division Allergologie\u2014Zentrale Methodenentwicklung, Paul-Ehrlich-Institute, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Raupach","sequence":"additional","affiliation":[{"name":"Research Group, Paul-Ehrlich-Institute, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirmal","family":"Adeel","sequence":"additional","affiliation":[{"name":"Research Group, Paul-Ehrlich-Institute, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Miller","sequence":"additional","affiliation":[{"name":"Research Group, Paul-Ehrlich-Institute, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Knapp","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, I. Department of Medicine, University Medical Center, Hamburg-Eppendorf, 20038 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-4863","authenticated-orcid":false,"given":"Christoph","family":"Welsch","sequence":"additional","affiliation":[{"name":"Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60329 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirco","family":"Glitscher","sequence":"additional","affiliation":[{"name":"Research Group, Paul-Ehrlich-Institute, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-4470","authenticated-orcid":false,"given":"Esra","family":"G\u00f6rg\u00fcl\u00fc","sequence":"additional","affiliation":[{"name":"Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60329 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Stoffers","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charit\u00e9 Mitte (CCM), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 13435 Berlin, Germany"},{"name":"Hasso-Plattner-Institute Digital Health Cluster, University Potsdam, 14471 Potsdam, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Lembeck","sequence":"additional","affiliation":[{"name":"Division Gastroenterology, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonel","family":"Trebicka","sequence":"additional","affiliation":[{"name":"Division Gastroenterology, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University Hospital Frankfurt, 60329 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai-Henrik","family":"Peiffer","sequence":"additional","affiliation":[{"name":"Division Gastroenterology, University Hospital M\u00fcnster, 48147 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eberhard","family":"Hildt","sequence":"additional","affiliation":[{"name":"Research Group, Paul-Ehrlich-Institute, 63225 Langen, Germany"},{"name":"Hasso-Plattner-Institute Digital Health Cluster, University Potsdam, 14471 Potsdam, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jhepr.2019.05.001","article-title":"The oncogenic role of hepatitis delta virus in hepatocellular carcinoma","volume":"1","author":"Villanueva","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/gut.46.3.420","article-title":"Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. 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